Hydrogen-rich water ameliorates bronchopulmonary dysplasia (BPD) in newborn rats

Abstract

Bronchopulmonary dysplasia (BPD) is characterized by developmental arrest of the alveolar tissue. Oxidative stress is causally associated with development of BPD. The effects of hydrogen have been reported in a wide range of disease models and human diseases especially caused by oxidative stress. We made a rat model of BPD by injecting lipopolysaccharide (LPS) into the amniotic fluid at E16.5. The mother started drinking hydrogen-rich water from E9.5 and also while feeding milk. Hydrogen normalized LPS-induced abnormal enlargement of alveoli at P7 and P14. LPS increased staining for nitrotyrosine and 8-OHdG of the lungs, and hydrogen attenuated the staining. At P1, LPS treatment decreased expressions of genes for FGFR4, VEGFR2, and HO-1 in the lungs, and hydrogen increased expressions of these genes. In contrast, LPS treatment and hydrogen treatment had no essential effect on the expression of SOD1. Inflammatory marker proteins of TNFα and IL-6 were increased by LPS treatment, and hydrogen suppressed them. Treatment of A549 human lung adenocarcinoma epithelial cells with 10% hydrogen gas for 24 hr decreased production of reactive oxygen species in both LPS-treated and untreated cells. Lack of any known adverse effects of hydrogen makes hydrogen a promising therapeutic modality for BPD. Pediatr Pulmonol. 2016; 51:928-935. © 2016 Wiley Periodicals, Inc.

Molecular hydrogen: a preventive and therapeutic medical gas for various diseases

“…Studies have also shown that H 2 improves lung injuries induced by many other factors, such as hyperoxia [ 163 , 164 ], lipopolysaccharides [ 14 , 17 ], smoke inhalation [ 165 ], paraquat[ 166 ], monocrotaline [ 167 ], and extensive burns [ 168 ]. A 2013 study showed that HS pretreatment ameliorated cigarette smoking-induced airway mucus production and airway epithelium damage in rats [ 169 ].…”

Expression levels of reactive oxygen species, NF-κBp65 and TGF-β1 and their correlations in bronchopulmonary dysplasia in neonatal rats

“…Under normal circumstances, excess ROS are neutralized in vivo by antioxidants such as glutathione peroxidase, superoxide dismutase and other antioxidant enzymes. It has been reported that lung injury may be associated with ROS [12,13]. It is known that NF-κBp65, which plays an important role in immune response, inflammatory response and apoptosis, is a transcription factor widely distributed in a variety of cells [14].…”

Recent Advances in Studies of Molecular Hydrogen against Sepsis

“…These lung protective effects are thought to be associated with a reduction in LPS-induced p38 mitogen-activated protein kinase (p38 MAPK) and c-Jun N-terminal kinase (JNK) activation by molecular hydrogen11, 14, 15. In addition to protecting the mature lung, HRS also alleviates bronchopulmonary dysplasia (BPD) induced by LPS in neonatal mice16. Fibroblast growth factor receptor 4 (FGFR4) and vascular endothelial growth factor receptor 2 (VEGFR2) are important for maintaining alveolar structures and lung development17, 18.…”

“…Fibroblast growth factor receptor 4 (FGFR4) and vascular endothelial growth factor receptor 2 (VEGFR2) are important for maintaining alveolar structures and lung development17, 18. Oral intake of HRS ameliorates LPS-induced suppression of genes encoding FGFR4, VEGFR2, and heme oxygenase 1 (HO-1) in neonatal mice16. In addition, study showed19 that LPS promotes the alveolar epithelial-mesenchymal transition (EMT) and pulmonary fibrosis by increasing the production of reactive oxygen species (ROS) and transforming growth factor-β (TGF-β).…”